2. Options B and B+: a simplified approach to integrated PMTCT & ART at the primary care level

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2 DraftforDiscussion For additional information on the paper, please contact: UNICEF (United Nations Children s Fund), Chewe Luo, cluo@unicef.org 1

3 DraftforDiscussion 1.0 Introduction 1. The global context The Global Plan towards the elimination of new HIV infections among children by 2015 and keeping their mothers alive is well underway, with ambitious goals of reducing the number of new HIV infections in children by 90% and HIV-related maternal deaths by 50%. 1 There is now unprecedented collaboration and political will to accomplish these goals, and many countries have made exceptional progress. According to UNAIDS estimates, in % of pregnant women living with HIV in low and middle-income countries received effective antiretroviral drugs for prevention of mother to child transmission (PMTCT), a substantial increase from 48% in Nonetheless, many implementation challenges remain, and chief among them is ensuring that high proportions of women and children in need of antiretroviral therapy (ART) can access it. Global access to ART among pregnant women in need was lower than access among adults in the general population at 34% vs. 47% in , far from the Global Plan target of 90% ART access by Low access of pregnant women to ART exists despite the fact that coverage of HIV testing is generally much higher in pregnant women than other adult populations. While poor ART access for pregnant women is a pervasive problem for many PMTCT programs, it disproportionately affects women and children living in areas far from ART sites or in settings with weak health systems. An AIDS-free generation is within reach. But to achieve this goal, all partners will need to redouble their efforts and boldly move forward, rather than shrinking back in the face of challenges. Reaching the hardest-to-reach women and children with ART will require thinking outside of the box to take implementation to a higher level of efficiency and effectiveness. Indeed, limited resources and pressing needs for broader maternal, neonatal and child health (MNCH) require that HIV programs maximize not only cost-effectiveness, but also benefits for other health programs. Clearly, a true game-changer is needed: an implementation modality for PMTCT that is at once both simpler and better than the current approaches. Is this possible? The great news is: yes! A new approach called Option B+ has already begun to show impressive results in real world, resource-constrained settings, dramatically increasing the numbers of pregnant women enrolling on ART. The tide is turning - now is the time to move with the momentum and embrace a bold public health approach to effectively eliminate new paediatric HIV infections. 2. Options B and B+: a simplified approach to integrated PMTCT & ART at the primary care level What are Options B and B+? Under WHO s 2010 PMTCT ARV guidance, countries had the option to choose between two prophylaxis regimens for pregnant women living with HIV with CD4 greater than 350 cells/mm 3 : Option A and Option B. 4 Under Option A, women receive antenatal and intrapartum antiretroviral prophylaxis along with an antiretroviral postpartum tail regimen to reduce risk of drug resistance, while infants receive postpartum antiretroviral prophylaxis throughout the duration of breastfeeding. Option B, on the other hand, has a simpler clinical flow in which all pregnant and lactating women with HIV initially are offered ART beginning in the antenatal period and continuing throughout the duration of breastfeeding. At the end of breastfeeding those women who do not yet require ART for their own health would discontinue the prophylaxis and continue to monitor their CD4 count, eventually re-starting ART when the CD4 falls below 350 cells/mm 3. Along with these two options a third approach is now being used, Option B+, in which all pregnant women living with HIV are offered life-long ART, regardless of their CD4 count. Table 1 below, adapted from WHO, summarizes these three different options. 2

4 DraftforDiscussion Treatment Table 1: Three Options for PMTCT 1 (for CD4 count < 350 cells/mm3) Prophylaxis (for CD4 count> 350 cells/mm3) Infant receives Option A Triple ARVs starting as soon as diagnosed, continued for life Antepartum: AZT starting as early as 14 weeks gestation Intrapartum: at onset of labour, single-dose NVP and first dose of AZT/3TC Postpartum: daily AZT/3TC through 7 days postpartum Daily NVP from birth until 1 week after cessation of all breastfeeding; or, if not breastfeeding or if mother is on treatment, through age 4 6 weeks Option B Triple ARVs starting as soon as diagnosed, continued for life Triple ARVs starting as early as 14 weeks gestation and continued intrapartum and through childbirth if not breastfeeding or until 1 week after cessation of all breastfeeding Daily NVP or AZT from birth through age 4 6 weeks regardless of infant feeding method Option B+ Triple ARVs starting as soon as diagnosed, continued for life Triple ARVs starting as soon as diagnosed, continued for life Daily NVP or AZT from birth through age 4 6 weeks regardless of infant feeding method Option B+ was first conceived and implemented in Malawi where the national ART program had already been functioning well using a public health approach which did not depend heavily on CD4 testing to determine who should initiate treatment. Malawi envisioned that Option B+ would be easier to implement due to its simple one size fits all approach which would enable women to access ART at high levels even in settings with poor access to CD4 testing. The early experience with Option B+ in Malawi has borne this out, being extraordinarily successful, with a more than fivefold increase in the numbers of pregnant women being enrolled on ART in only the first quarter of full nationwide implementation. 5 6 Importantly, implementation of Option B+ in Malawi involved much more than a change in antiretroviral regimen. Option B+ was part of a larger strategy in which Malawi s ART and PMTCT programs fully integrated with one another so that ART could be administered by nurses at primary care facilities where women and children were already accessing MNCH services. Using this equity-focused approach, Malawi has been able to rapidly expand access to ART for pregnant women in hard-to-reach areas throughout the country. In April 2012, in response to Malawi s early success and other strategic and technical developments, WHO released an important programmatic update on the Use of Antiretroviral Drugs for Treating Pregnant Women and Preventing HIV Infection in Infants 7 in which it urged countries to consider what the advantages of Options B and B+ may be in their contexts, stating: Options B and specifically B+ seem to offer important programmatic and operational advantages and thus could accelerate progress towards eliminating new paediatric infections. Along with discussing the potential operational benefits due to greater simplicity of Option B and B+, WHO s programmatic update also emphasizes that Option B+ in particular may have significant additional advantages beyond PMTCT. These include providing better protection for maternal health and greater reduction 1 This table is adapted in a slightly modified form from a Table 1 in WHO s 2012 programmatic update: Use of Antiretroviral Drugs for Treating Pregnant Women and Preventing HIV Infection in Infants, available at 3

5 DraftforDiscussion in the sexual transmission of HIV than other options. While acknowledging the additional cost of Option B+ in terms of drugs, WHO notes that the cost of a simplified first-line once-daily regimen of efavirenz/tdf/3tc has decreased substantially, and that the overall cost-effectiveness of Option B and B+ are likely to be greater than Option A. However, the update also makes it clear that adopting Option B or B+ is no easy fix for PMTCT, and that ultimate success of Option B+ in particular will require an increased investment in interventions to improve long-term ART adherence and retention. Intensified support is also needed for other aspects of PMTCT programs beyond ART, including ensuring support for safe breastfeeding for HIV-exposed infants. Importantly, the WHO update also highlights how options B and B+ fit into larger HIV initiatives and opportunities. Adoption of Option B/B+ could streamline monitoring and evaluation of progress on implementation of the Global Plan and simplify procurement and supply chain management, as most countries move to a single drug regimen for PMTCT and 1 st line ART. Additionally, Option B, and especially B+, creates the opportunity to implement on a wide scale WHO/UNAIDS Treatment 2.0 strategy of the radical simplification of HIV treatment 8, through decentralizing ART to the primary care level and task-shifting to nurses and other cadres. Related to this, implementing Options B and B+ provides an excellent opportunity to begin rolling-out of treatment as prevention, which can have a significant impact in reducing new HIV infections due to sexual transmission among serodiscordant partners. But along with great potential of Option B/B+ to impact a wide-range of HIV objectives, it is also critical not to overlook the unprecedented opportunities that implementation of Option B/B+ will provide to strengthen broader MNCH services, including optimal infant feeding practices for HIV free survival of HIV-exposed infants and young children. The provision of life-long ART to women, children, and family members through the very same primary care facilities that provide MNCH services means that over time a very larger fraction of all ART patients will receive treatment at these facilities. ART programs and MNCH programs therefore need to come together like never before so that both can be successful. As part of this new level of collaboration, ART resources, which represent the lion s share of HIV funding in many countries, should be invested more intensively in strengthening the health systems that support MNCH services. This can lead to a broad and sustainable improvement in health for all women, children, and their family members. 3. Purpose of this document The potential for PMTCT to have a profound impact on the HIV epidemic and broader maternal and child health has never been clearer and more compelling. In response to these tremendous opportunities and also to WHO s recent programmatic update, this document is meant primarily to help countries that desire to be ahead of the curve and begin the process of preparing to adopt Option B or B+ now. The document therefore contains considerations on key policy, programmatic and partnership issues that relate to implementation of Option B or B+. Planning well to address these key issues can hopefully help countries hit the ground running and avoid unnecessary bottlenecks in rolling-out Option B or B+. This document does not provide new formal guidance, but rather discusses technical considerations that are relatively broad in scope, so that different country contexts can adapt the advice to their more specific needs. Additionally, as was suggested in the WHO programmatic update, it is hoped that as countries consider what is a best fit for their context, valuable lessons will be learned that can be shared more broadly and feed into the global revisions of HIV recommendations by WHO in

6 DraftforDiscussion While this document may contain helpful advice for any country considering adopting Option B or B+, it especially focuses on the advantages of Option B+ in high and intermediate prevalence countries, urging such countries to consider adopting an implementation model of nurse-initiated ART in MNCH settings. This document draws to some extent on the early experience of Malawi, the first low-income country to successfully begin implementation of Option B+ on a nationwide scale. 4. Target audiences of this document This document is intended primarily for use by national governments and their partners at the country-level. Although it is meant primarily to aid the decision-making processes at the countrylevel, other multi-national partners in the public and private sector may also find it helpful to better understand the challenges countries may be facing. In particular, multi-national partners may find the last section of the document useful in envisioning how they might better focus support to countries to help make the most of an investment in Option B+. 5. Overview of this document In addition to this introductory section, the document contains four other sections: Section 2, The Rationale for Option B+: Full integration and Simplification at the Primary Health Care Level, provides an explanation of how Option B+ can be a critical component of a larger simplified approach of implementation of ART within primary care facilities that provide MNCH services, in line with the principles of WHO/UNAIDS Treatment 2.0 initiative. Through such an equity-focused public health approach, fully integrated PMTCT and ART services can efficiently reach the lowest level of the health system. Section 3, Key Considerations for Policies and Processes : Building Consensus at the Country Level, provides suggestions for processes and criteria that countries can use to help build broad consensus on important issues related to ART for pregnant and lactating women. This includes bigpicture issues such as whether to adopt Option B/B+ and with it a simplified approach to ART- PMTCT implementation at the primary care level. More specific technical issues are also discussed for countries to consider in formulating policies related to Option B/B+. Section 4, Key Considerations for Program Planning: Bringing ART into MNCH Settings and Bringing Women and Children to the Services, is meant to inform implementation plans of those countries that ultimately choose to adopt Option B/B+. It emphasizes a model of nurse-administered ART at primary care facilities, outlining important considerations for programs as they seek to bring integrated ART-PMTCT services to the most vulnerable women and children. Section 5, Key Considerations for Partnerships: Making the Most of a Tremendous Opportunity to Improve the Health of Women and Children, discusses how to ensure that an investment in ART for all pregnant women yield returns far beyond PMTCT. To broaden, maximize, and sustain impact, partnerships will be crucially important with other health programs, technological innovators, people living with HIV, and local communities. For more specific discussion of the relative technical and business merits of Options A, B and B+, readers should see the aforementioned WHO s April 2012 programmatic update on Option B/B+ as well as UNICEF/Business Leadership Council s A Business Case for Options B and B+ to Eliminate Mother-to-Child Transmission of HIV by

7 DraftforDiscussion 2.0 The Rationale for Option B+: Full Integration and Simplification at the Primary Health Care Level In attempting to attain high-levels of coverage of women and children with ART and other necessary interventions, PMTCT programs have frequently been plagued by what has come to be known as the PMTCT cascade. The PMTCT cascade refers to the loss-to-follow-up (LTFU) that occurs throughout the antenatal, intrapartum, and postnatal periods at various points along the continuum of care. Since women and children access HIV services through MNCH platforms, improving retention along the continuum of care will require not only HIV-specific interventions, but also addressing larger structural bottlenecks, including especially the weak linkages between HIV and MNCH services and systems that exist in many settings. Demand-side bottlenecks also need to be addressed, as women are often not well informed of what services they should receive, why these services are important, or where and when they can access them. While PMTCT services have by necessity been implemented within MNCH settings, ART services have generally not been. Therefore, it is perhaps not surprising that the gulf within the continuum of care between ART services and MNCH services has been particularly glaring in many cases. However, as described below, implementation of Option B+ can provide an opportunity to address some of these structural and demand-side bottlenecks in the continuum of care, by bringing ART, PMTCT, and MNCH services together for fuller integration. As part of these efforts, investing in the MNCH platform will continue to be critical, as MNCH remains the gateway by which women and children access PMTCT and ART services. 1. Full Integration of PMTCT and ART services and programs is needed Why has increasing access to ART among pregnant women been so challenging in many settings? One key reason is that PMTCT services and ART services have often operated in largely separate, vertical fashion, being poorly integrated with regard to their location, providers, and timing. With regard to location, ART services are typically not available in all lower-level clinics, whereas in many countries some form of PMTCT services, including ARVs, have scaled up to most, if not all, primary health care centers that provide antenatal and broader MNCH services. With regard to providers, nurses, who are the primary providers of PMTCT services, have not yet begun to initiate ART in many of the primary health care facilities where women come for MNCH services. Low availability of ART at MNCH sites results in particularly poor access to ART for the most vulnerable women and children, as many would have to travel long distances from their homes to access ART at higherlevel facilities. Even when women are able to reach these facilities, poor coordination with respect to the timing of service delivery can be a bottleneck to access. While ART in pregnant women should be initiated as soon as possible to minimize the risks of infant infections and maternal mortality, ART clinics are often not organized to give priority to pregnant women. Delays related to scheduling, laboratory testing, or adherence counseling often preclude ART from starting until later in gestation or after birth. In addition to the need for better integration of services, there is also a pressing need for full integration of the larger PMTCT and ART programs. This includes management and supervision, financing, laboratory systems, supply chain management, and monitoring and evaluation. Although ART programs have typically had much greater funding than PMTCT programs, they have rarely focused on reaching pregnant women as a core objective, leaving most of the responsibility for addressing this critical gap to PMTCT programs. PMTCT programs, on the other hand, have struggled to develop effective referral systems to ART sites, establish lab transport networks, and extend a reliable supply chain of antiretroviral drugs to the very large number of primary care MNCH facilities that they must support. These difficulties have been compounded by the fact that PMTCT 6

8 DraftforDiscussion and ART monitoring systems are usually separate and poorly linked, resulting in widespread difficulties measuring and reporting on the number of pregnant women initiating ART an indicator that is fundamental for measuring progress. Training and supervision of PMTCT and ART providers is also often uncoordinated, and the overall management of the two programs is sometimes not fully unified, with ART tending to have a higher political profile and stronger leadership. The poor integration of PMTCT and ART programs and services cannot be accepted as the status quo, as it leads to very inefficient use of resources and highly inequitable access to services for the most vulnerable women and children. ART and PMTCT services need to be co-located and administered by nurses and midwives at the primary care level where women and children are already accessing other MNCH services. And ART and PMTCT programs need to join together to strengthen the health system so that it can efficiently serve the hardest-to-reach women and children. 2. Simplification of ART and PMTCT interventions is also critically important However, full integration of ART and PMTCT will not be sufficient alone to bring implementation to a higher level of efficiency and effectiveness. Further simplification of the PMTCT and ART interventions themselves is also a critically enabling factor to enable fully integrated PMTCT and ART services to be provided at the primary level of care. First, the antiretroviral regimen in general and the antiretroviral drug prophylaxis regimen for PMTCT in particular need to be simplified. As outlined earlier, of the two choices in WHO s 2010 PMTCT recommendations, Option A is clearly more complicated than Option B, in requiring maternal antenatal and intrapartum antiretroviral prophylaxis, a different antiretroviral postpartum tail to reduce risk of drug resistance, and postpartum antiretroviral prophylaxis to infants throughout the duration of breastfeeding. Furthermore, under Option A those mothers who do require treatment for their own health begin lifelong antiretroviral therapy with a different drug regimen. In contrast, under Option B, a single preferred antiretroviral regimen can be used for all women. Therefore, while both Option A and Option B have comparable and very high individual level efficacy, resulting in <5% vertical transmission rates in clinical trials conducted in relatively well-resourced and controlled environments 10, the real world operational public health effectiveness for Option A and Option B may be quite different from one another due to the greater simplicity of Option B, especially in the context of a weak health system. While in its 2010 guidance WHO noted the potential advantage of Option B s simplicity in administration, at the time the guidance was issued there was little real world country data yet to compare the effectiveness of the two options, since the clinical trials had only recently been completed. Therefore, the great majority of high-burden countries made decisions to adopt Option A, given the lower costs of drug regimen per pregnant woman treated. However, as implementation has progressed and the enrollment of pregnant women on ART has continued to lag, it has become apparent that the complexity of implementing Option A is a key bottleneck that is contributing to slower progress than desired. However, while Option B is clearly simpler than Option A with respect to the drug regimen, the laboratory and timing requirements of both options complicate implementation. Both require CD4 testing to identify who needs life-long treatment, and this has been a major barrier to access in many settings, especially in hard-to-reach areas, but even to a surprising degree in higher-level health facilities. Additionally, although all women start out with the same regimen under Option B, those who do not yet require ART for their own health must stop it for a period of time after the cessation of breastfeeding. This complicates implementation, requiring a system to confirm breastfeeding has stopped, transfer out a fraction of women from the ART program, keep these women in follow-up, and then re-start them on ART at some point in the future. Furthermore, especially given the high 7

9 DraftforDiscussion fertility rates that exist in many countries with high HIV prevalence, option B would effectively require that some women start and stop ART multiple times over the course of several pregnancies. Equity requires that we seek to reach the hardest-to-reach women, children, and families first. While, well-resourced higher-level facilities and centers of excellence may have had some degree of success in implementing Option A or Option B, even these facilities have typically had extreme difficulty obtaining the 90% ART coverage target among pregnant women living with HIV in need of treatment recommended in the Global Plan. To reach all women and children in need, and especially the most vulnerable, the currently complex PMTCT and ART interventions need to be greatly simplified, effectively merging into a single intervention for pregnant women. 3. Option B+: full integration and simplification at the primary health care level The good news is that a fully integrated and simplified approach to PMTCT and ART has now begun to be implemented successfully on a large scale. As mentioned earlier, Option B+ provides a potentially better alternative to Option A or Option B through which all pregnant women living with HIV can initiate ART for life regardless of CD4 count. After an in-country consultation to assess the feasibility of Option A and Option B, Malawi concluded that neither would be best for its country context, choosing instead Option B+, for reasons which have been outlined in detail elsewhere. 11 From a health systems standpoint, Option B+ streamlines PMTCT by enabling simplification of the supply chain, monitoring systems, and program management. At the service delivery level, Option B+ also streamlines implementation with a one-size-fits-all approach that is easy for patients and providers to understand. Through making a positive HIV test the only condition necessary to initiate ART, Option B+ makes it feasible to implement the most effective PMTCT interventions for mother and child at the smallest and most remote health centers, thereby ensuring that lack of access to CD4 testing does not prohibit women from receiving needed treatment. Additionally, Option B+ also provides a straightforward approach to postnatal follow-up that can be integrated with efforts to help women safely breastfeed their infants. And, by avoiding the start-stop-start approach that would be required with option B for many women who might have more than one pregnancy, Option B+ makes it easy to convey clear public health message to all people in the community that ART, once started, needs to be adhered to for life. Furthermore, Option B+ offers additional potential health benefits, including reduction in sexual transmission of HIV and improved maternal health. It is important to recognize that Malawi s decision to adopt Option B+ involved embracing much more than a change in an antiretroviral drug regimen. Rather, Malawi rightly saw that what was called for was simplification and integration of PMTCT and ART programs, services, and interventions on every level. The leadership of the two programs therefore joined together, revising the national guidelines, supply chain, monitoring and evaluation, and human resources strategies and plans for both PMTCT and ART. Full integration also occurred at the service delivery level, as Malawi utilized an equity-focused approach of nurse-administered ART in all facilities providing MNCH services, thereby making the services available to women and children close to where they live and without requiring referral out to other facilities. Malawi also capitalized on the opportunity to integrate HIV interventions with other services in MNCH facilities, for example by integrating the routine offer of family planning into the standard package of ART follow-up for all women initiating Option B+. 8

10 DraftforDiscussion As mentioned earlier, the initial experience with implementation of Option B+ in Malawi, which began nationwide in late 2011, has been very positive, with a more than 5-fold increase in the quarterly number of pregnant women initiating ART as compared to before Option B+ was implemented (7,218 in Q vs. 1,257 Q2 2011) 12. In the first full quarter of implementation of Option B+ at all MNCH facilities, pregnant or lactating women represented ~40% of all new patients initiating ART (14,017 out of 34,669) 13. As a result, the total numbers of all patients initiating ART in the national program increased by an astounding 88% after implementation of Option B+ for only one quarter. While these dramatic proportions are expected to decrease somewhat in future quarters after an initial backlog of women have all enrolled on Option B+, it is still predicted that almost 25% of all people newly initiating ART in Malawi will be pregnant once the system reaches steady state. As countries respond to the recent WHO programmatic update and consider whether to adopt Option B or B+, they can be encouraged by Malawi s initial success. While each country context will be different, Malawi s experience provides a public health proof-of-concept, demonstrating the dramatic benefits that can come about in part through adopting one simplified regimen for all women in PMTCT. A simpler regimen can open up a new world of possibility in terms of how and where ART can be implemented, making it much more feasible to implement ART at the lowest level of the health system. However, it would be misguided to conclude from this success that a change in regimen alone will be the panacea for the problems of PMTCT. Malawi s early success has been the result of a number of synergistic factors coming together, including strong leadership, a fully integrated approach to ART and PMTCT, and an equity-focused strategy of nurse-initiated ART within primary care facilities. Nevertheless, while Option B/B+ is not a PMTCT panacea, it is likely 9

11 DraftforDiscussion one essential component of a highly efficient and simplified modality of PMTCT-ART implementation at the primary care level. However, it is also important to recognize that long-term success with Option B+ for Malawi and other countries will not only depend on the ability to initiate high numbers of pregnant women on ART, but also to retain them on life-long ART. 10

12 DraftforDiscussion 3.0 Key Considerations for Processes and Policies: Building Consensus at the Country Level Since the beginning of widespread implementation of PMTCT in low and middle-income countries about a decade ago, there have been multiple changes in recommended prophylaxis regimens, beginning with short course AZT and single-dose nevirapine, followed by the 2006 WHO guidelines which recommended more effective regimens for prophylaxis and ART for the pregnant women with CD4 less than 200, and then the 2010 guidelines recommending Option A or Option B for prophylaxis and a CD4 cut off of less than 350 for life-long ART. With each change in guidelines, substantial transaction costs have occurred, including revising guidelines, retraining of providers, adapting monitoring and evaluation systems, and developing new plans for procurement and supply chain management. It is understandable that countries may be weary of the many changes, and perhaps even hesitant to consider making further policy changes in response to the 2012 WHO programmatic update. However, on the positive side, those countries that begin the discussion now about transitioning to Option B+ can be energized by the realization that once Option B+ is adopted the basic approach of treating all pregnant women living with HIV is not likely to change again soon. If countries plan well for this transition, they can move forward focusing on how to continuously improve their PMTCT and ART programs, rather than being preoccupied by which antiretroviral regimen to use. This includes focusing on optimal infant feeding practices and improving routine postnatal follow-up for both mothers and infants. Seen in this light, Option B+ offers a great opportunity to focus on implementation with a long-term view, optimizing systems that can be used for many years to come. With this in mind, the following section outlines key processes that countries may find helpful in coming to consensus about whether to adopt Option B or B+, and also outlining some key policy issues that may need to be addressed if the decision is made to move from Option A to Option B or B+. 1. Foster collaboration of PMTCT, ART, and other health programs Cultivating a collaborative and inclusive environment is important throughout the process of coming to consensus at the country level about whether and how to adopt Option B/B+. In most countries structures exist which provide technical guidance and oversight for PMTCT and ART implementation, often called technical working groups (TWGs), though the nomenclature differs from country to country. While PMTCT and ART technical structures are often somewhat separate from one another, in order for countries to move forward effectively for full integration of PMTCT and ART, it is critical that these two technical structures collaborate very closely, if not merge into a single group. In the case of Malawi, the ART and PMTCT TWGs effectively merged with one another in order to conduct a feasibility assessment of different PMTCT regimen options. After the decision to adopt B+ as a regimen, these groups continued to operate as one unit in planning for the roll-out of the implementation of ART in all facilities providing MNCH services. 14 Such high-level integration of the technical leadership and management functions of PMTCT and ART programs is likely a prerequisite to seeing subsequent full integration of these services at the primary health care level. The ART-PMTCT technical structures should also be as inclusive as possible with regard to bringing other stakeholders into their deliberations. This includes health care workers with real world implementation experience at the facility level, technical advisors from international agencies, women, including mothers, living with HIV, and experts from other health program areas, such as MNH, family planning, infant feeding and nutrition, and child health. 11

13 DraftforDiscussion In most countries different levels of cooperation exist between HIV and other health programs, such as MNCH and family planning. However, in some cases there may be a history of competition for limited resources or even some tension between different program areas. In light of this reality, other stakeholders beyond the HIV program may approach the possibility of providing antiretroviral therapy for all women in PMTCT with some skepticism or even opposition. A reflex reaction may be to oppose such a policy based upon fears that it will further drain human and financial resources away from under-supported MNCH and FP programs. Rather than ignoring such concerns or moving into a competitive mode, the HIV program would be wise to respond in a spirit of true collaboration, recognizing that HIV programs now have clearer shared interests with MNCH programs than ever before. HIV treatment of all pregnant women would mean a very large fraction of patients starting ART will be initiating services within MNCH clinics and will be followed-up at the primary health care level. The ART program therefore needs the MNCH clinics to function well. Recognizing this reality HIV, MNCH, and family planning programs can come together to brainstorm about how to use this opportunity to collaborate more intentionally. (See Section 5.1 for more on this subject) 2. Rapidly assess PMTCT progress, focusing on ART access and equity As a first step to inform the discussion about whether to adopt Option B or B+, countries may find it helpful to rapidly assess their current PMTCT progress. An in-depth and time-consuming review of national program may not be necessary, and indeed would not be advisable in most cases, as this could lead to unnecessary delays. Rather than muddle the picture by looking at too many details, program should hone in on a few core indicators to honestly take stock of performance. In making such a rapid assessment, arguably the most critical criteria to examine is what proportion of pregnant women in need of ART in a given country, state, region/province, district, or facility are accessing ART. 2 This is a clear and simple barometer of how well the PMTCT program is doing, and data should be readily available for this indicator (though unfortunately in many cases it may not be - which in and of itself would be a strong indication that change is urgently needed!) Importantly, countries should evaluate ART access for pregnant women on a sub-national level through an equity-lens, seeking to determine whether the hardest-to-reach women are accessing ART, or whether, as is often the case, the pregnant women who are accessing ART disproportionately hail from certain areas of the country or facilities with better access to resources. Programs should examine both the numbers and proportions of pregnant women accessing ART, as well as the types and locations of facilities that are providing ART for pregnant women. If ART services are predominantly relegated to higher level facilities, urban areas, and centers of excellence supported by external partners, this should be a sign that change is needed. As part of the process of analyzing access of pregnant women to ART, programs are also highly encouraged to examine ART access for infants and children. In addition to looking at quantitative data, programs may want to incorporate qualitative feedback from health workers and end-users if possible. This information may be readily available from recent site visits that have been conducted as part of regular supervision or program reviews, or perhaps could be rapidly obtained via a survey of a few health workers using mobile phones or other means. Health workers and women living with HIV can be asked simple questions focused on what is working and what is not working with regard to ART access for pregnant women and children. They can also be queried about whether they believe it is realistic to expect to reach the MTCT initiative 2 The number of pregnant women in need of ART can be roughly estimated in a given area (i.e. district, facility) by multiplying the estimated antenatal HIV prevalence applicable to that local area X the number of pregnancies per year X 40%, which is roughly the proportion of pregnant women living with HIV that qualify for treatment with a CD4 cut-off of

14 DraftforDiscussion target of 90% of pregnant women in need receiving ART using their current ARV prophylaxis regimen (i.e. Option A or B) and approaches to implementation. After completing such a rapid assessment, countries will likely fall mainly into two categories. A few countries which are implementing Option A may find that they are on track with respect to their PMTCT and ART goals and targets. As WHO noted in its April 2012 programmatic update, such countries do not necessarily need to prioritize switching from Option A to Option B or B+, at least in the short term. On the other hand, many countries will likely find their current progress is far off track with respect to reaching pregnant women with ART. For these countries, major changes should be considered, including adopting Option B or B+. 3. Come to consensus on optimal modalities of PMTCT-ART service delivery Before proceeding to decide on a specific drug regimen (i.e. A, B, B+), it is advisable to come to consensus on what mode of implementation of ART is best fit to the particular goals and context of a country. The mode of implementation includes where ART for pregnant women will be implemented (location), who will initiate it (providers), and when ART will be offered to women (timing). With regard to location, several models are possible including location of ART services within the same MNCH clinic that provides PMTCT ( fully integrated location); ART services located in a separate building or section within the same overall health care facility as PMTCT; (so-called proximal partially integrated 15 location); or ART services in a separate health facility than the PMTCT services ( not integrated location). With respect to providers, options include ART initiated by physicians only or ART-initiated by other cadres as well, including nurses/midwives and clinical officers. And with respect to timing, possible models include timing of the ART visit being coordinated with ANC and MNCH visits in the postnatal period versus relatively uncoordinated (i.e. ART is only offered at certain days or times that does not necessarily overlap with ANC or other MNCH visits). Evidence supports what common sense would also seem to indicate - that implementation of ART for pregnant women within MNCH clinics can result in much higher levels of uptake than when women are referred out to other sites, such as for example ART clinics at higher level facilities which tend to be more distant from where women live. A cluster-randomized trial in Zambia showed that the provision of ART in MNCH facilities approximately doubled the uptake of ART by pregnant women compared to when ART was provided by out-referral. 16 Other programmatic experience also strongly supports the contention that providing ART within MNCH can increase ART uptake compared to referring out to other sites. Indeed, even when pregnant women are referred out from MNCH clinics to separate ART clinics within the same facility, such as often occurs in large hospital settings, these referrals can be associated with high rates of LTFU. 17 Therefore, it is advisable, at least in most high HIV prevalence settings, to aim to initiate ART for pregnant women in the same facilities that provide MNCH services, and in the same clinical space whenever possible. While co-location of PMTCT-ART services for pregnant women is important, it is generally not sufficient for optimizing ART-PMTCT uptake. For example, in one observational study, there was little difference between uptake among three clinics using a full-integrated, partially integrated, and un-integrated location of ART-PMTCT services. 18 In this case, though the clinic had an integrated location, different providers were providing ART and PMTCT services (physicians vs. nurses) and at different scheduled times. This underlines the importance of integrating all three aspects of services - location, providers, and timing to maximize the likelihood of pregnant women initiating ART. Indeed, arguably the most critical ingredient of the Malawi s early success with Option B+ is that Malawi chose to implement ART in all sites providing MNCH services, with nurses initiating ART in a coordinated fashion with ANC visits. 13

15 DraftforDiscussion Given that space and staffing in MNCH is often limited, hybrid models can also be considered in which ART is initiated by nurses in MNCH, but women are carefully transitioned at some point after delivery, to another clinical space where lifelong ART can continue to be provided, preferably, though not necessarily, in the same facility. The optimal timing and location of transition from PMTCT to a separate long-term ART program will vary somewhat based upon the specific characteristics of sites within a country, though in most cases it will likely be preferable to transition after weaning. Along with coming to consensus about the preferred modality of ART initiation and follow-up of pregnant mothers, it is also important to agree on the recommended mode of follow-up of HIVexposed and infected infants and young children. In countries where ART will be initiated in primary care facilities that provide MNCH services, it is logical for the same health care workers and clinics providing ART for the mother to be given the core responsibility of ensuring HIV-exposed and infected infants receive the necessary interventions in the postnatal period. This includes early infant diagnosis, support for breastfeeding and nutrition, cotrimoxazole, nevirapine or zidovudine prophylaxis for the first 4-6 weeks after birth, and, for those infants who are infected, timely ART. Given the number of different interventions that HIV-exposed and infected infants require, it is important that there is a home at the facility where the needed care and longitudinal follow-up is coordinated. A family-centered approach in which mothers and infants have the same home for care has been implemented successfully in many contexts, and this model also offers the potential to bring male partners in for testing and treatment. A single mode of implementation for reaching mothers and children will probably not be a good fit for every facility in a given country. However, it may be helpful for each country to come to consensus about the predominant mode of implementation it will use to reach all pregnant women in need of ART and to provide the needed services for HIV-exposed and infected children. Overall, in order to maximize equity, population-based coverage, and effectiveness it is strongly recommended that countries with intermediate and high HIV prevalence consider an approach that emphasizes nurseadministered ART and paediatric care in primary health care facilities that provide MNCH services. It is important to allow for the fact that provision of ART within such facilities may not be practical in some contexts, particularly low prevalence settings where very small proportions of women are HIVpositive. However, if ART is not provided in the same clinics or facilities where women test positive, active, timely referrals need to be implemented to ensure that pregnant women start ART as soon as possible after diagnosis and are not LTFU. An active referral means that the referring site takes responsibility for ensuring the referral is accomplished, for example by accompanying the pregnant women to the ART clinic and systematically verifying that ART was initiated Compare the operational effectiveness of Options A, B and B+ Once consensus has been reached about what the main mode of implementation should be for a country s goals and context, the next step is to come to agreement on what the form of PMTCT-ART protocol (Option A, B, or B+) is a best fit for this mode of implementation. Operational effectiveness is a broad term that encompasses both the feasibility of implementation in real world clinical environments as well as broader health system issues that relate to the scalability of an intervention to achieve high population-based coverage. WHO s recent programmatic update has already stated that Options B and especially Option B+ are likely to have greater operational effectiveness due to greater simplicity than Option A. With this helpful guidance, countries can move forward to validate whether Option B or B+ is likely to be operationally superior in their context. 3 Indeed, it is clear that adopting Option B/B+ in settings where ART is not provided on at the same site where HIV testing occurs could be highly problematic without such active referral systems in place. In such cases, if women are referred out to an ART clinic, but not given any antiretroviral prophylaxis, Option B/B+ could have unintended negative consequences in reducing access to prophylaxis for PMTCT 14

16 DraftforDiscussion Now that countries have been implementing Option A or Option B for some time, they have the advantage of having data to better inform a comparison between Option A, B, and B+. However, since a country is typically implementing only one of these three options, the evaluation of how well other options that are not actually being implemented might function will have to depend to a large extent on expert opinion, estimates, and educated judgments. Countries may not need to do an indepth assessment that would involve gathering new data, but in most cases may be able to estimate what the comparative effectiveness of implementing the three regimens (A, B, and B+) might be in their context based upon existing data and experience. Estimating a range of what proportion of pregnant women would be able to access ART using either option A, B, or B+ may be helpful, and can also be useful in later comparison of incremental cost-effectiveness (see Section 3.7 below) Malawi s experience shows that such consultative processes, though they are less definite in some ways than a formal evaluation, observational study, or comparative clinical trial, can nevertheless be extremely useful. In comparing the projected feasibility of implementing different PMTCT regimens in its context, Malawi conducted a consultation, using information from its current programs to identify key bottlenecks that it saw with regard to Options A and B. For Option A, Malawi had already found that implementing a combination PMTCT regimen in the antenatal and intra-partum periods was challenging. Many health providers and patients both had difficulty understanding the complexity of the different drug regimens, including which drugs should be taken and when. And in considering Option B, Malawi noted that lack of wide availability of quality assured CD4 testing was a major bottleneck to women accessing ART. Furthermore, for both Option A and Option B, Malawi s consultation noted that telling some women to stop ART after breastfeeding could lead to confusion in the community about the need for life-long adherence to ART. In light of these considerations and others, strong consensus was reached that option B+ was best for Malawi. A similar process may be helpful in enabling other countries to come to broad agreement about which regimen to use. Table 2 below outlines some inter-related elements that countries might consider in comparing the operational effectiveness of the three options. Table 2: Comparing the Operational Effectiveness of Options A, B, and B+ Key Element Laboratory requirements Simplicity for providers Equity Timing-dependence Follow-up pathway(s) Dependence on breastfeeding duration Supply chain Monitoring and evaluation Adherence messages Integration Suitability Community Engagement Questions to Consider Is the regimen dependent on high access to CD4 testing to function effectively? Is the regimen easy for nurses and other providers to understand and implement? Can the regimen be effectively provided in hard-to-reach areas, with marginalized communities, and at the lowest level of the health system? Is implementation of the regimen dependent on timing, including starting and stopping drugs at different times and/or specific timing of labs? How will mothers and children be followed on the different regimens? Is a single, streamlined follow-up pathway possible? Does implementation of the regimen cease at the cessation of breastfeeding? If so how will it be verified that women have stopped breastfeeding? How complicated are the supply chain requirements for the regimen? Can the supply chain easily be integrated with the ART supply chain? How straightforward is it to monitor and evaluate receipt of the regimen? Can M&E systems for the regimen be integrated with those for the ART program? What adherence messages and support need to be provided with the regimen? Are these consistent with those of the national ART program? How easy will it be to integrate the regimen within MNCH, ART, and family planning platforms and services? What are the structures in place in health facilities and community systems (e.g. church, traditional, networks of people living with HIV) for demand creation and service delivery support? 15